The Clinical Application Value Of HPV DNA Testing Of Sentinel Lymph Nodes In Early Cervical Cancer

Background and ObjectiveCervical cancer is one of the most common malignancy in women and is also the only preventable malignancy with clear etiology.The incidence is closely related to persistenthigh-risk human papilloma virus(HPV)infection.Lymph node metastasis(LNM)is a ·high risk factor affecting the prognosis of cervical cancer.The International Federation of Gynecology and Obstetrics in 2018 for cervical cancer staging proposed:all stages on the basis of gynecological examination,can be complemented by an assessment of tumor size and extent based on imaging and pathology,and LNM(including imaging and pathology)can be included as one of the criteria for clinical staging.Cervical cancer is mainly treated by surgery and radiotherapy,supplemented by chemotherapy,in recent years,immunotherapy has also been gradually applied in clinical practice.Surgery is the main treatment option for patients with early cervical cancer(ECC)(stage ⅠA to ⅡA),and ovarian and vaginal function preservation is an option for younger patients.To avoid relapse or metastasis caused by LNM after the surgery,pelvic lymph node dissection(PLND)was listed as an important component of cervical cancer surgery.Nevertheless,The incidence of LNM in early cervical cancer is low,and PLND is prone to lead to lower limb edema,lymphatic retention,immunocom promise and other complications,which affects the quality of life.Therefore,early cervical cancer patients with routine pelvic lymph nodes dissection exists the possibility of excessive treatment.In 2014,the National Comprehensive Cancer Network(NCCN)guidelines for cervical Cancer suggested that sentinel lymph node biopsy should be considered for some patients with early cervical cancer(including stage ⅠA,stage ⅠB1,and stage ⅡA1)(Level 2B evidence),Which can avoid unnecessary pelvic lymph node dissection to improve the quality of life of patients after surgery without affecting prognosis.Sentinel lymph nodes(SLN)are defined as the first stage of lymphatic drainage of primary malignant tumor and can reflect the metastatic status of regional lymph nodes.In theory,if there is no metastasis in SLN,then there will be no metastasis in other lymph nodes.At present,clinically,it is believed that sentinel lymph node is the first lymph node with developped after the injection of sentinel lymph node tracer.However,routinely pathological detection in cliniconly can detect lymph node metastasis with a diameter of more than 2mm,while metastasis with a diameter of under 2mm is often ignored and show false negative.Sentinel lymph node biopsy has not been used as a routine surgical method in clinic due to the limitation of the technology of mapping and intraoperative pathological detection.In recent years,studies have shown that the positivity of HPV DNA in lymph nodes is closely related to lymph node metastasis,and HPV DNA detection in lymph nodes can detect micrometastasis that are not detected by conventional pathologic test.Integrate the above research and theory,the clinical application of the HPV DNA detection of sentinel lymph node in ECC has important research value.Our study mainly carried out HPV DNA detection of SLN,to analyed the relationship between the presence of HPV DNA in SLN and LNM,the influencing factors of LNM and the influence of HPV DNA positivity in SLN on prognosis,and to explore the clinical value of HPV DNA detection of sentinel lymph node in ECC.Materials and MethodsThe 119 early cervical cancer patients who received SLN procedureand radical hysterectomy in the First Affiliated Hospital of Zhengzhou University from December 2017 to November 2019 were selected as the research subjects.SLNs developed intraoperatively were detected by PCR for HPV DNA,and all lymph nodes removed were sent to the pathology department for routine pathological examination.Then patients were followed up by medical records or telephone after surgery every three months.Collate the basic information and clinical data of patients(name,age,contact number,previous medical history,clinical stage,surgical method,HPV infection type of primary cervical cancer,postoperative pathological results,HPV DNA test results of SLN and so on).SPSS 21.0 statistical software was used for statistical analysis,and the test level a was 0.0.5.Results1 General situation and follow-up of the patientsA total of 119 patients with ECC were selected in this study,with an average age of(49.9±9.6)years.By February 2021,the median follow-up time was 23 months(0-37 months),among which,4 patients were lost to follow-up,2 patients died of other diseases,2 patients died of uncontrolled disease,2 patients had multiple metastases,3 patients had pelvic relapse,and the rest of the patients lived without disease.2 The satuation of SLN detection and the results of HPV DNA testOf 119 ECC patients who suffered SLN procedure,108 patients were developed with SLN,11 patients were undeveloped with SLN,with an development rate of 90.8%.Of 108 patients who underwent HPV DNA testing for SLN,44 patients were HPV DNA positive and 64 patients were HPV DNA negative.And the HPV type of all SLN patients with HPV DNA positive of SLN was consistent with the HPV infection type of primary cancer.3 Analysis of HPV DNA and lymph node metastasis of SLNThe 108 ECC patients who underwent HPV DNA testing of SLN were divided into two groups according to the results of HPV DNA testing of SLN.44 patients were HPV DNA positive in SLN,of which 13 patients were SLN metastatic positive,and the rate of SLN metastatic positive was 29.5%(13/44).There were 64 cases of HPV DNA negative in SLN,of which 3 cases were positive for SLN metastasis,and the positive rate of SLN metastasis was 4.7%(3/64).The difference in the positive rate of SLN metastasis between the two groups was statistically significant(P=0.000).4 Analysis of HPV DNA test of SLN and routine pathological examination of the whole pelvic lymph nodesAmong 44 cases of HPV DNA positive of SLN,16 cases were positive for PLN metastasis,the positive rate of PLN metastasis was 36.4%(16/44).Among the 64 HPV DNA negative patients of SLN,6 cases were positive for PLN metastasis,and the positive rate of SLN metastasis was 9.4%(6/64).The positive rate of PLN metastasis between the two groups was statistically significant(P=0.000).The sensitivity,negative predictive value(NPV)and false negative rates of HPV DNA detection in sentinel lymph nodes for PLN metastasis were 72.7%(16/22),90.6%(58/64)and 9.4%(6/64),respectively.5 Analysis of influencing factors of LNM and the sensitivity of SLN to HPV DNA testingConsidered the clinical characteristics of the patie nts,and combined with the statistical analysis,we found that Clinical stage,tumor tissue type,intrauterine invasion,HPV infection type,age and other factors had no significant influence on lymph node metastasis.And tumor size,depth of invasion,degree of differentiation,lymph-vascular space Invasion and HPV DNA positivity of SLN were the influencing factors for LNM,and HPV DNA positivity of SLN was an independent influencing factor for LNM.These above clinical features had no significant effect on the sensitivity of HPV DNA test for SLN to predict LNM.6 The influence of HPV DNA positivity in SLN on disease free survivalIn the group without lymph node metastasis,28 ECC patients were HPV DNA positive in SLNs and 58 ECC patients were HPV DNA negative in SLNs.There was no significant difference in disease-free survival between the two groups(P=0.177).Conclusion(1)The positive of HPV DNA in SLN is an independent influencing factor for LNM,which can be used as a predictor for evaluating LNM and has a guiding significance for surgical plan and postoperative adjuvant treatment.(2)The accuracy of HPV DNA test in SLN for evaluating LNM was not affected by tumor size,invasion depth and other factors.(3)The positive of HPV DNA in SLN had no significant effect on the DFS of patients with early cervical cancer.